Skip to main content

Advertisement

SpringerLink
Log in

Targeting cleavage and polyadenylation specific factor 1 via shRNA inhibits cell proliferation in human ovarian cancer

  • Published:
Journal of Biosciences Aims and scope Submit manuscript

Abstract

Cleavage and polyadenylation specificity factor 1 (CPSF1), a member of CPSF complex, has been reported to play a key role in pre-mRNA 3′-end formation, but its possible role in ovarian cancer remains unclear. In the present study, we found the mRNA level of CPSF1 was overexpressed in ovarian cancer tissues using Oncomine Cancer Microarray database. Then the loss-of-function assays, including CCK-8, colony formation and flow cytometry assays, were performed to determine the effects of CPSF1 on cell viability, proliferation, cell cycle and apoptosis of human ovarian cancer cell lines (SKOV-3 and OVCAR-3). The results indicated that depletion of CPSF1 suppressed cell viability, impaired colony formation ability, induced cell cycle arrest at G0/G1 phase and promoted cell apoptosis in ovarian cancer cells. Furthermore, knockdown of CPSF1 upregulated the expression of cleaved caspase-3 and PARP and downregulated CDK4/cyclin D1 expression. These data suggested that CPSF1 could promote ovarian cancer cell growth and proliferation in vitro and its depletion might serve as a potential therapeutic target for human ovarian cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  • Aragaki M, Takahashi K, Akiyama H, Tsuchiya E, Kondo S, Nakamura Y and Daigo Y 2011 Characterization of a cleavage stimulation factor, 3’ pre-RNA, subunit 2, 64 kDa (CSTF2) as a therapeutic target for lung cancer. Clin. Cancer Res. 17 5889–5900

    Article  CAS  PubMed  Google Scholar 

  • Bolli N, Payne EM, Rhodes J, Gjini E, Johnston AB, Guo F, Lee JS, Stewart RA, Kanki JP and Chen AT 2011 cpsf1 is required for definitive HSC survival in zebrafish. Blood 117 3996–4007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bonome T, Levine DA, Shih J, Randonovich M, Pise-Masison CA, Bogomolniy F, Ozbun L, Brady J, Barrett JC, Boyd J and Birrer MJ 2008 A gene signature predicting for survival in suboptimally debulked patients with ovarian cancer. Cancer Res. 68 5478–5486

    Article  CAS  PubMed  Google Scholar 

  • Calzado MA, Sancho R and Munoz E 2004 Human immunodeficiency virus type 1 Tat increases the expression of cleavage and polyadenylation specificity factor 73-kilodalton subunit modulating cellular and viral expression. J. Virol. 78 6846–6854

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen W, Guo W, Li M, Shi D, Tian Y, Li Z, Wang J, Fu L, Xiao X, Liu QQ, Wang S, Huang W and Deng W 2013 Upregulation of cleavage and polyadenylation specific factor 4 in lung adenocarcinoma and its critical role for cancer cell survival and proliferation. PLoS One 8 e82728

    Article  PubMed  PubMed Central  Google Scholar 

  • Cools J, Stover EH, Wlodarska I, Marynen P and Gilliland DG 2004 The FIP1L1-PDGFRalpha kinase in hypereosinophilic syndrome and chronic eosinophilic leukemia. Curr. Opin. Hematol. 11 51–57

    Article  CAS  Google Scholar 

  • Danckwardt S, Hentze MW and Kulozik AE 2008. “3’ end mRNA processing: molecular mechanisms and implications for health and disease. EMBO J. 27 482–498

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dominski Z, Yang XC, Purdy M, Wagner EJ and Marzluff WF 2005 A CPSF-73 homologue is required for cell cycle progression but not cell growth and interacts with a protein having features of CPSF-100. Mol. Cell Biol. 25 1489–1500

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gotlib J, Cools J, Malone JM 3rd, Schrier SL, Gilliland DG and Coutre SE 2004 The FIP1L1-PDGFRalpha fusion tyrosine kinase in hypereosinophilic syndrome and chronic eosinophilic leukemia: implications for diagnosis, classification, and management. Blood 103 2879–2891

    Article  CAS  PubMed  Google Scholar 

  • Heintz AP, Odicino F, Maisonneuve P, Beller U, Benedet JL, Creasman WT, Ngan HY and Pecorelli S 2003 Carcinoma of the ovary. Int. J. Gynaecol. Obstet. 83 135–166

    Article  PubMed  Google Scholar 

  • Hendrix ND, Wu R, Kuick R, Schwartz DR, Fearon ER and Cho KR 2006 Fibroblast growth factor 9 has oncogenic activity and is a downstream target of Wnt signaling in ovarian endometrioid adenocarcinomas. Cancer Res. 66 1354–1362

    Article  CAS  PubMed  Google Scholar 

  • Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D 2011 Global cancer statistics. CA Cancer J. Clin. 61 69–90

    Article  PubMed  Google Scholar 

  • Karst AM and Drapkin R 2010 Ovarian cancer pathogenesis: a model in evolution. J. Oncol. 2010 932371

    Article  PubMed  Google Scholar 

  • Keller W, Bienroth S, Lang KM and Christofori G 1991 Cleavage and polyadenylation factor CPF specifically interacts with the pre-mRNA 3’ processing signal AAUAAA. EMBO J. 10 4241–4249

    CAS  PubMed Central  Google Scholar 

  • Kiefer H, Mizutani A, Iemura S, Natsume T, Ando H, Kuroda Y and Mikoshiba K 2009 Inositol 1,4,5-triphosphate receptor-binding protein released with inositol 1,4,5-triphosphate (IRBIT) associates with components of the mRNA 3’ processing machinery in a phosphorylation-dependent manner and inhibits polyadenylation. J. Biol. Chem. 284 10694–10705

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kleiman FE and Manley JL 2001 The BARD1-CstF-50 interaction links mRNA 3’ end formation to DNA damage and tumor suppression. Cell 104 743–753

    Article  CAS  PubMed  Google Scholar 

  • Koga M, Satoh T, Takasaki I, Kawamura Y, Yoshida M and Kaida D 2013 U2 snRNP is required for expression of the 3’ end of genes. Plos One 9 e98015

    Article  Google Scholar 

  • Legge F, Ferrandina G, Salutari V and Scambia G 2005 Biological characterization of ovarian cancer: prognostic and therapeutic implications. Ann Oncol 16(Suppl 4) iv95–101

  • Lu KH, Patterson AP, Wang L, Marquez RT, Atkinson EN, Baggerly KA, Ramoth LR, Rosen DG, Liu J, Hellstrom I, Smith D, Hartmann L, Fishman D, Berchuck A, Schmandt R, Whitaker R, Gershenson DM, Mills GB and Bast RC Jr 2004 Selection of potential markers for epithelial ovarian cancer with gene expression arrays and recursive descent partition analysis. Clin. Cancer Res. 10 3291–3300

    Article  CAS  PubMed  Google Scholar 

  • Murthy KG and Manley JL 1995 The 160-kD subunit of human cleavage-polyadenylation specificity factor coordinates pre-mRNA 3’-end formation. Genes Dev. 9 2672–2683

    Article  CAS  PubMed  Google Scholar 

  • Rozenblatt-Rosen O, Nagaike T, Francis JM, Kaneko S, Glatt KA, Hughes CM, LaFramboise T, Manley JL and Meyerson M 2009 The tumor suppressor Cdc73 functionally associates with CPSF and CstF 3’ mRNA processing factors. Proc Natl Acad Sci U S A 106 755–760

    Article  CAS  PubMed Central  Google Scholar 

  • Siegel RL, Miller KD and Jemal A 2016 Cancer statistics, 2016. CA Cancer J. Clin. 66 7–30

    Article  Google Scholar 

  • Steinman RA 2007 mRNA stability control: a clandestine force in normal and malignant hematopoiesis. Leukemia 21 1158–1171

    Article  CAS  PubMed  Google Scholar 

  • Topalian SL, Kaneko S, Gonzales MI, Bond GL, Ward Y and Manley JL 2001 Identification and functional characterization of neo-poly(A) polymerase, an RNA processing enzyme overexpressed in human tumors. Mol. Cell Biol. 21 5614–5623

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang Q and Doublie S 2011 Structural biology of poly(A) site definition. Wiley Interdiscip. Rev. RNA 2 732–747

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ye D, Luo H, Lai Z, Zou L, Zhu L, Mao J, Jacob T, Ye W, Wang L and Chen L 2016 ClC-3 chloride channel proteins regulate the cell cycle by up-regulating cyclin D1-CDK4/6 through suppressing p21/p27 expression in nasopharyngeal carcinoma cells. Sci. Rep. 6 30276

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Intervention Therapy, Jilin Cancer Hospital, Changchun, Jilin, China

    Beiguang Zhang, Ying Liu & Donghui Liu

  2. Department of Radiology, Jilin Cancer Hospital, Changchun, Jilin, China

    Lei Yang

Authors
  1. Beiguang Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ying Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Donghui Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lei Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lei Yang.

Additional information

Corresponding editor: Sorab Dalal

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, B., Liu, Y., Liu, D. et al. Targeting cleavage and polyadenylation specific factor 1 via shRNA inhibits cell proliferation in human ovarian cancer. J Biosci 42, 417–425 (2017). https://doi.org/10.1007/s12038-017-9701-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12038-017-9701-x

Keywords

Search

Navigation